Control of biocatalytic transformations by programmed DNA assemblies

This study demonstrates the self-assembly of inhibitor/enzyme-tethered nucleic acid fragments or enzyme I-, enzyme II-modified nucleic acids into functional nanostructures that lead to the controlled inhibition of the enzyme or the activation of an enzyme cascade. In one system, the anti-cocaine aptamer subunits are modified with monocarboxy methylene blue (MB⁺) as the inhibitor and with choline oxidase (ChOx). The cocaine-induced self-assembly of the aptamer subunits complex results in the inhibition of ChOx by MB ⁺. In a further configuration, two nucleic acids of limited complementarity are functionalized at their 3′ and 5′ ends with glucose oxidase (GOx) and horseradish peroxidase (HRP), respectively, or with MB⁺ and ChOx. In the presence of a target DNA sequence, synergistic complementary base-pairing occurs, thus leading to stable supramolecular Yshaped nanostructures of the nucleic acid units. A GOx/HRP bienzyme cascade or the programmed inhibition of ChOx by MB⁺ is demonstrated in the resulting nucleic acid nanostructures. A quantitative theoretical model that describes the nucleic acid assemblies and that results in the inhibition of ChOx by MB⁺ or in the activation of the GOx/HRP cascade, respectively, is provided.